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Biomedical subjects

J Hudson

Publications and source records attributed to J Hudson.

At least 37 records · Page 2Linked to original sources
PubMed2000

What kinds of people should we create?

The advent of genetic engineering will give people the power to design the members of the succeeding generation, and thus will render practical the issue how such a power ought to be exercised. Here I address that issue in a general way. I point out that the aim of making future people better adapted to the modern social environment is implicitly circular, since the natures of the peoples themselves will determine the nature of the social environment. I claim that the human property the enhancement of which would do most to enrich experience is intelligence; accordingly increased intelligence should be a primary aim of genetic designers. The tendency to feel pain should be attenuated, as positive motivation is substituted for negative (to some extent). People should be designed so as to be motivated more by reason than by any non-rational drives (though rational motivation may still involve pleasure and pain). The sex drive, having outlived its usefulness, will probably be replaced by some other source of pleasure. As a side effect of these changes in people, the arts and social sciences will be transformed beyond recognition.

Genetic Engineering↗
PubMed2000

A cluster of pediatric metallic mercury exposure cases treated with meso-2,3-dimercaptosuccinic acid (DMSA)

Nine children and their mother were exposed to vapors of metallic mercury. The source of the exposure appears to have been a 6-oz vial of mercury taken from a neighbor's home. The neighbor reportedly operated a business preparing mercury-filled amulets for practitioners of the Afro-Caribbean religion Santeria. At diagnosis, urinary mercury levels in the children ranged from 61 to 1,213 microg/g creatinine, with a geometric mean of 214.3 microg/m creatinine. All of the children were asymptomatic. To prevent development of neurotoxicity, we treated the children with oral meso-2,3-dimercaptosuccinic acid (DMSA). During chelation, the geometric mean urine level rose initially by 268% to 573.2 microg mercury/g creatinine (p<0.0005). At the 6-week follow-up examination after treatment, the geometric mean urine mercury level had fallen to 102.1 microg/g creatinine, which was 17.8% of the geometric mean level observed during treatment (p<0.0005) and 47.6% of the original baseline level (p<0.001). Thus, oral chelation with DMSA produced a significant mercury diuresis in these children. We observed no adverse side effects of treatment. DMSA appears to be an effective and safe chelating agent for treatment of pediatric overexposure to metallic mercury.

Administration, Oral↗
PubMed2000

Factors affecting metamotivational reversals during motor task performance.

Reversal theory proposes that the individual's psychological state constantly switches between metamotivational state pairs (such as Apter's 1982 telic-paratelic pair). Three factors are thought to affect reversals: frustration, contingent event, and satiation. Only a few studies have directly investigated these factors in sports contexts, and evidence is needed to assess support for these factors. In a laboratory setting, 24 participants performed a telic and a paratelic version of a dart-throwing task for 10 min. Participants were free to change from one task version to another as they wished, and reasons for any task changes were solicited. Task changes, indicative of reversals, were observed in 11 participants, and these were reported as due to satiation or frustration but not to contingent events. These findings may inform the structure of sessions on skill development but require confirmation in actual sports contexts.

Achievement↗
PubMed2000

Development of a prostate cDNA microarray and statistical gene expression analysis package.

A cDNA microarray comprising 5184 different cDNAs spotted onto nylon membrane filters was developed for prostate gene expression studies. The clones used for arraying were identified by cluster analysis of > 35 000 prostate cDNA library-derived expressed sequence tags (ESTs) present in the dbEST database maintained by the National Center for Biotechnology Information. Total RNA from two cell lines, prostate line 8.4 and melanoma line UACC903, was used to make radiolabeled probe for filter hybridizations. The absolute intensity of each individual cDNA spot was determined by phosphorimager scanning and evaluated by a bioinformatics package developed specifically for analysis of cDNA microarray experimentation. Results indicated 89% of the genes showed intensity levels above background in prostate cells compared with only 28% in melanoma cells. Replicate probe preparations yielded results with correlation values ranging from r = 0.90 to 0.93 and coefficient of variation ranging from 16 to 28%. Findings indicate that among others, the keratin 5 and vimentin genes were differentially expressed between these two divergent cell lines. Follow-up northern blot analysis verified these two expression changes, thereby demonstrating the reliability of this system. We report the development of a cDNA microarray system that is sensitive and reliable, demonstrates a low degree of variability, and is capable of determining verifiable gene expression differences between two distinct human cell lines. This system will prove useful for differential gene expression analysis in prostate-derived cells and tissue.

DNA, Complementary↗
PubMed1999

Serotonergic function in cocaine addicts: prolactin responses to sequential D,L-fenfluramine challenges.

BACKGROUND: Preclinical studies have shown that cocaine produces alterations in serotonergic function but our knowledge of the serotonergic alterations due to cocaine abuse in humans is still fragmentary. We therefore assessed the central serotonergic responsivity of cocaine addicts and control subjects by neuroendocrine challenges with the serotonin releaser and reuptake inhibitor D,L-fenfluramine (FEN). METHODS: Plasma prolactin levels following a 60 mg oral dose of FEN and placebo were studied in 25 hospitalized male cocaine addicts and 13 healthy male subjects. Control subjects underwent one set of FEN/placebo challenges and cocaine addicts two sets of challenges, during the first and third weeks following cocaine discontinuation. Patients were divided into two subgroups as a function of presence (FH+) and absence (FH-) of a paternal history of substance abuse. The following comparisons were made: 1) Control subjects versus entire patient group and versus patient subgroups; 2) entire patient group and patient subgroups responses to first versus second challenges; 3) FH+ versus FH- patients' early responses and FH+ versus FH- patients' late responses. RESULTS: The prolactin responses to FEN increased significantly in the entire patient group as time following cocaine discontinuation increased. The FH+ patients had significantly blunted early responses by comparison with FH- patients and control subjects. There was a more pronounced rebound of the responses of FH+ patients by comparison with those of FH- patients. As a result, comparisons of the late responses of FH+ and FH- patients and of FH+ patients and control subjects became nonsignificant. CONCLUSIONS: Cocaine use appears to have an effect on the serotonergic mechanisms mediating prolactin release in humans. In the present study, this effect was more pronounced in a subgroup of patients with a paternal history of alcoholism or drug abuse. The greater blunting of the prolactin response observed within days of cocaine discontinuation followed by a greater rebound of this response 2 weeks later could indicate an increased vulnerability to the disruptive effects of cocaine in these patients.

Administration, Oral↗
PubMed1999

Spermiogenesis is impaired in mice bearing a targeted mutation in the protein phosphatase 1cgamma gene.

Type 1 protein phosphatases (PP1) are involved in diverse cellular activities, ranging from glycogen metabolism to chromatin structure modification, mitosis, and meiosis. The holoenzymes are composed of two or more subunits, including a catalytic subunit (PP1c) and one or more regulatory subunits. Many eukaryotes possess several catalytic subunit genes which encode highly conserved isoforms. In rodents, one of these isoforms, PP1cgamma2, appears to be expressed predominantly in testes. Whether PP1cgamma2 performs a testis-specific function is unclear. To address this and other questions, the PP1cgamma gene was disrupted by targeted insertion in murine embryonic stem cells. Mice derived from these cells were viable, and homozygous females were fertile. However, males homozygous for the targeted insertion were infertile. Histological examination revealed severe impairment of spermiogenesis beginning at the round spermatid stage. In addition, defects in meiosis were inferred from the presence of polyploid spermatids. Immunohistochemistry revealed the presence of PP1calpha protein on condensing spermatids in both wild-type and mutant testes, suggesting that this closely related isoform is unable to compensate for the loss of PP1cgamma. These defects are discussed in the light of known functions of protein phosphatase 1.

Animals↗
PubMed1999

The transcriptional program in the response of human fibroblasts to serum.

The temporal program of gene expression during a model physiological response of human cells, the response of fibroblasts to serum, was explored with a complementary DNA microarray representing about 8600 different human genes. Genes could be clustered into groups on the basis of their temporal patterns of expression in this program. Many features of the transcriptional program appeared to be related to the physiology of wound repair, suggesting that fibroblasts play a larger and richer role in this complex multicellular response than had previously been appreciated.

Blood↗
PubMed1998

A physical map of 30,000 human genes.

A map of 30,181 human gene-based markers was assembled and integrated with the current genetic map by radiation hybrid mapping. The new gene map contains nearly twice as many genes as the previous release, includes most genes that encode proteins of known function, and is twofold to threefold more accurate than the previous version. A redesigned, more informative and functional World Wide Web site (www.ncbi.nlm.nih.gov/genemap) provides the mapping information and associated data and annotations. This resource constitutes an important infrastructure and tool for the study of complex genetic traits, the positional cloning of disease genes, the cross-referencing of mammalian genomes, and validated human transcribed sequences for large-scale studies of gene expression.

Animals↗
PubMed1998

Does the Composite International Diagnostic Interview underdiagnose the eating disorders?

OBJECTIVE: A study was undertaken to assess the procedural validity of the Composite International Diagnostic Interview (CIDI) for the diagnosis of eating disorders. METHOD: The CIDI was administered to 44 patients consecutively admitted to an eating disorders unit. CIDI-generated diagnoses were compared with clinical diagnoses documented in patient files. Discrepancies between diagnoses were examined in detail. RESULTS: A significant level of disagreement was apparent, particularly for anorexia nervosa patients. A large number of patients with symptoms requiring inpatient treatment did not reach criteria using CIDI's diagnostic algorithm. CONCLUSION: Considerable difficulties remain in the use of standardized assessments, such as the CIDI, to diagnose eating disorders. While presenting features of the illness, for example, ego syntonic nature of the illness, secrecy, and denial, may be part of the reason, the questions used by the CIDI appear to be in need of some refinement.

Anorexia Nervosa↗
PubMed1998

Measurement of elastic-like behaviour in the power squat.

Because traditional procedures of evaluating elastic-like behaviour have yielded mixed results, the purpose of this work was to explore two methods of measuring elastic-like behavior in the power squat. The entire concentric time method was based on traditional procedures. The initial concentric time method was developed to examine elastic-like behavior for the beginning 0.2 s of concentric movement. The present study compares a power squat performed maximally by nine subjects at 70% of their 1 repetition maximum. Squats were performed with rebound (REB) and without rebound (NRB). For the entire concentric time method only concentric time was significantly greater (p < 0.05) in the NRB than the REB. For the initial concentric time method the relative displacement, velocity, net work, & peak power of the center of mass were significantly greater (p < 0.05) in the REB than the NRB. Some subjects had theoretically infeasible negative results for elastic enhancement in the entire concentric time method, but not the initial concentric time method. It seems that measuring elastic-like behavior near the end of the movement can be confounded by the constraints of the task. Based on its success, the initial concentric time method appears to be more appropriate for measurement of elastic-like behavior in lifting.

Adult↗
PubMed1998

The cdr2(+) gene encodes a regulator of G2/M progression and cytokinesis in Schizosaccharomyces pombe.

Schizosaccharomyces pombe cells respond to nutrient deprivation by altering G2/M cell size control. The G2/M transition is controlled by activation of the cyclin-dependent kinase Cdc2p. Cdc2p activation is regulated both positively and negatively. cdr2(+) was identified in a screen for regulators of mitotic control during nutrient deprivation. We have cloned cdr2(+) and have found that it encodes a putative serine-threonine protein kinase that is related to Saccharomyces cerevisiae Gin4p and S. pombe Cdr1p/Nim1p. cdr2(+) is not essential for viability, but cells lacking cdr2(+) are elongated relative to wild-type cells, spending a longer period of time in G2. Because of this property, upon nitrogen deprivation cdr2(+) mutants do not arrest in G1, but rather undergo another round of S phase and arrest in G2 from which they are able to enter a state of quiescence. Genetic evidence suggests that cdr2(+) acts as a mitotic inducer, functioning through wee1(+), and is also important for the completion of cytokinesis at 36 degrees C. Defects in cytokinesis are also generated by the overproduction of Cdr2p, but these defects are independent of wee1(+), suggesting that cdr2(+) encodes a second activity involved in cytokinesis.

ATP-Binding Cassette Transporters↗
PubMed1998

Accuracy of medical records in hip fracture.

OBJECTIVE: To determine the accuracy of diagnoses and procedure codes in medical records for hip fracture patients. DESIGN: A validation sample of hip fracture medical records was used to compare the facesheet data with progress notes, operative reports, and discharge summaries for patients in a prospective study of functional recovery. SETTING: Eight Baltimore hospitals with the highest volume of older hip fracture patients. PATIENTS: Study subjects were 343 community-dwelling patients, 65 years of age and older, admitted to one of eight Baltimore hospitals between January 1990 and June 1991 with a diagnosis of hip fracture. MAIN OUTCOME MEASURES: Facesheet diagnosis codes were compared with admitting notes, discharge summary, and/or progress notes. The abstracted surgical procedure was compared with postoperative radiographs. RESULTS: Excess coding of diagnoses on the hospital facesheet was evident in 12% of charts. In 17% of charts, a complication identified in the chart was not coded on the facesheet. More complications with low severity were omitted. Agreement between the abstractor's procedure review and radiograph readings for arthroplasty was 84%. In 15% of patients, the abstractor coded total arthroplasty when hemiarthroplasty was done. CONCLUSIONS: Discrepancy between the hospital facesheet and the medical record and between the abstracted surgical procedure and radiographs was found for hip fracture patients. This may make findings from health outcomes research relying on administrative databases uncertain and reimbursement inaccurate.

Aged↗
PubMed1998

Outcome after hemiarthroplasty for femoral neck fractures in the elderly.

A prospective outcome study was performed on 270 patients, 65 years of age and older, who sustained a femoral neck fracture and underwent hemiarthroplasty. The treatment compared was the use of a noncemented unipolar versus either a cemented or a press fit bipolar prosthesis. The outcome variables assessed included the occurrence of a postoperative complication, length and cost of hospitalization, and function in various quality of life measurements. Patients who underwent bipolar hemiarthroplasty with either a cemented or a press fit prosthesis had better pain relief and function than patients who had a noncemented unipolar prosthesis at a minimum of 24 months after surgery. However, the mean hospitalization cost for patients who had a bipolar prosthesis was $12,290 compared with $8876 for a unipolar prosthesis.

Activities of Daily Living↗
PubMed1998

Effect of fenfluramine challenge on cocaine craving in addicted male users.

The authors studied the effects of a challenging dose of the serotonin (5-HT)-releaser/reuptake inhibitor d,l-fenfluramine (FEN) on spontaneous cocaine craving in a group of cocaine-addicted users in order to evaluate the involvement of serotonergic pathways in the modulation of craving for cocaine. Nineteen cocaine-dependent male inpatients received 60 mg of FEN or placebo (double-blind). Data were compared with those obtained in a previous study of another serotonergic probe, the partial postsynaptic agonist meta-chlorophenyl-piperazine (m-CPP). FEN significantly reduced cocaine craving and increased cortisol and prolactin when compared with placebo. When the responses to the two drugs were compared, there were no differences in the cortisol and prolactin rises, but m-CPP was a more potent inhibitor of cocaine craving than FEN. These data suggest that 5-HT releasers/reuptake inhibitors and serotonergic agents with greater postsynaptic activity should be further examined.

Adult↗
PubMed1997

The meta-chlorophenylpiperazine challenge test in cocaine addicts: hormonal and psychological responses.

We report on the neuroendocrine and psychological responsivity of 31 cocaine addicts and 14 controls to the serotonergic agonist, meta-chlorophenylpiperazine (m-CPP) (0.5 mg/kg p.o.). Cocaine addicts were subdivided into subjects with aggressive tendencies and other features similar to those found in type 2 alcoholics and subjects without these features. Following m-CPP, aggressive and nonaggressive patients had a significantly blunted prolactin response compared to controls, but there was no difference between the two patient subgroups. There was no difference between the cortisol responses of nonaggressive patients and controls, but aggressive patients had a significantly blunted cortisol response compared to controls and nonaggressive patients. Both patient subgroups reported more intense "activation-euphoria" and "high" responses following m-CPP than controls. These results could indicate the existence of alterations along serotonergic pathways in cocaine addicts taken as a group. In addition, a subgroup of patients who could be described as type 2 cocaine addicts appear to be biologically different from healthy subjects and from other cocaine addicts as indicated by a greater cortisol blunting following m-CPP.

Adult↗
PubMed1997

Safety and immunogenicity of UBI HIV-1MN octameric V3 peptide vaccine administered by subcutaneous injection.

Twenty-four HIV-seronegative men, at high risk of HIV infection, were recruited into a phase I/II safety and immunogenicity trial of a prototype HIV vaccine. The immunogen was a synthetic, monovalent, octameric HIV-1MN V3 peptide in an aluminum hydroxide (alum) adjuvant. The vaccine had been evaluated previously using a standard 0-, 1-, 6-month intramuscular schedule and was found to stimulate neutralizing antibody in 60-90% of volunteers. Participants were randomized to receive either 500 micrograms (n = 10; high dose) or 100 micrograms (n = 10; low dose) of immunogen or placebo (alum alone; n = 4) at 0, 1, and 6 months by subcutaneous injection. Responses to the immunogen were evaluated by enzyme-linked immunosorbent assay (ELISA)-detectable antibody and by proliferative responses. Safety was monitored by both clinical assessment and regular review with a clinical psychologist. No serious adverse experiences were observed following administration of the assigned medication. One individual (placebo) seroconverted while on study, following exposure to HIV. After the vaccination course only four individuals (three high dose and one low dose) had ELISA-detectable antibody against the immunogen. In the evaluable samples, from 19 volunteers, only 7 vaccine recipients (3 high dose and 4 low dose) had demonstrable lymphoproliferative responses to preparations of the immunogen. Subcutaneous administration of its candidate vaccine was safe but did not result in uniform or robust immunological responses.

AIDS Vaccines↗